Role of neutralizing anti-murine interleukin-17A monoclonal antibody on chronic ozone-induced airway inflammation in mice.

Abstract

Exposure to ozone has led to airway inflammation and airway hyperresponsiveness, which potential mechanisms relate to ozone-induced oxidative stress. IL-17 is a growing target for autoimmune and inflammatory diseases. The aim of the study was to examine the inhibitory effects of anti-murine interleukin-17A monoclonal antibody (IL-17mAb) on adverse effects of ozone which are noted above. After C57/BL6 mice were exposed to ozone (2.5ppm; 3h) for 12 times over 6 weeks, IL-17mAb, PBS was intraperitoneally injected into mice 1h after ozone or air exposure for 6 weeks and mice were studied 24h after final exposure, monitoring bronchial responsiveness, airway inflammatory cells, lung histology, levels of neutrophil-related chemokine and proinflammatory cytokines in bronchoalveolar lavage (BAL) fluid and serum, the expression of IL-17A mRNA and protein, glucocorticoid receptors (GR), and the phosphorylation of p38MAPK in lung tissues. The administration of IL-17mAb reduced the ozone-induced increases in total cells, especially neutrophils; decreased levels of cytokines, including IL-8 in BAL fluid, IL-8 and IL-17A in serum; mitigated the severity of airway hyperresponsiveness; attenuated lung inflammation scores and histologic analysis confirmed the suppression of lung inflammation, compared with the administration of a control PBS. Exposure to ozone results in increases in IL-17A production rate, mRNA and protein levels of IL-17A and the protein level of GR. These effects were halted and reversed by IL-17mAb treatment. Furthermore, IL-17mAb also reduced the phosphorylation of p38MAPK. Therefore, we conclude that IL-17mAb may be a useful therapy in ozone-related diseases, including COPD.

• Authors: Min Zhang, Xia Fei, Guo-Qing Zhang, Peng-Yu Zhang, Feng Li, Wu-Ping Bao, Ying-Ying Zhang, Xin Zhou
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 83 Pg. 247-256 (Oct 2016) ISSN: 1950-6007 [Electronic] France
• PMID: 27380433 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neutralizing
• Cytokines
• Interleukin-17
• RNA, Messenger
• Ozone

Topics

• Animals
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Antibodies, Neutralizing (pharmacology, therapeutic use)
• Bronchi (drug effects, pathology)
• Bronchoalveolar Lavage Fluid (cytology)
• Cell Count
• Chronic Disease
• Cytokines (blood)
• Emphysema (blood, drug therapy, pathology, physiopathology)
• Interleukin-17 (genetics, immunology, metabolism)
• Male
• Mice, Inbred C57BL
• Ozone
• Pneumonia (blood, drug therapy, pathology, physiopathology)
• RNA, Messenger (genetics, metabolism)